ROS-induced biodegradable polythioketal nanoparticles for intracellular delivery of anti-cancer therapeutics

Jee Seon Kim; Sung Duk Jo; Geok Leng Seah; Insu Kim; Yoon Sung Nam

Journal of Industrial and Engineering Chemistry, Vol.21, 1137-1142, January, 2015

DOI10.1016/j.jiec.2014.05.026 Export Citation

ROS-induced biodegradable polythioketal nanoparticles for intracellular delivery of anti-cancer therapeutics

Jee Seon Kim¹, Sung Duk Jo², Geok Leng Seah¹, Insu Kim¹, and Yoon Sung Nam^{1, 3, †}

¹Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea
²Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea
³Department of Biological Sciences, KAIST Institute for NanoCentury (CNiT), KAIST Institute for BioCentury, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea

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This study introduces biodegradable poly(1,4-phenyleneacetone dimethylene thioketal) (PPADT) nanoparticles as an intracellular delivery carrier for anti-cancer therapeutic applications. PPADT is synthesized through condensation polymerization of 2,2-dimethoxypropane and 1,4-benzenedimethanethiol. The synthesized PPADT is used to prepare polymeric nanoparticles encapsulated with Nile red or paclitaxel. The presence of reactive oxygen species (ROS) facilitates the polymer degradation via breakage of the thioketal bonds, resulting in disruption of the nanoparticle structure and release of the encapsulated molecules. Therapeutic effects of the paclitaxel-loaded PPADT nanoparticles are demonstrated using PC-3 prostate cancer cells, while no significant cytotoxic effects of placebo PPADT nanoparticles are observed. Our study suggests that ROS-sensitive biodegradable PPADT nanoparticles can be a new promising material for intracellular drug delivery of insoluble drugs.

Keywords:Poly(thioketal);Nanoparticles;Paclitaxel;Biodegradable;Cancer

[References]

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Shim MS, Xia Y, Angew. Chem.-Int. Edit., 52, 6926 (2013)
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[1] Oh JE, Nam YS, Lee KH, Park TG, J. Control. Release, 57, 269 (1999)

[2] Nam YS, Song SH, Choi JY, Park TG, Biotechnol. Bioeng., 70(3), 270 (2000)

[3] Cho KY, Choi SH, Kim CH, Nam YS, Park TG, Park JK, J. Control. Release, 76, 275 (2001)

[4] Park TG, Lee HY, Nam YS, J. Control. Release, 55, 181 (1998)

[5] Nam YS, Park TG, J. Biomed. Mater. Res., 47, 8 (1999)

[6] Nam YS, Park TG, J. Microencapsul., 16, 16 (1999)

[7] Gopferich A, Biomaterials, 17, 103 (1996)

[8] Tian HY, Tang ZH, Zhuang XL, Chen XS, Jing XB, Prog. Polym. Sci, 37, 237 (2012)

[9] Wilson DS, Dalmasso G, Wang LX, Sitaraman SV, Merlin D, Murthy N, Nat. Mater., 9(11), 923 (2010)

[10] Shukla AK, Verma M, Singh KN, Indian J. Chem. B, 43, 1748 (2004)

[11] Bae KH, Lee JY, Lee SH, Park TG, Nam YS, Adv. Healthc. Mater., 2, 576 (2013)

[12] Oh MH, Kim JS, Lee JY, Park TG, Nam YS, RSC Adv., 3, 14642 (2013)

[13] Lee JY, Bae KH, Kim JS, Nam YS, Park TG, Biomaterials, 32, 8635 (2011)

[14] Lee H, Lee K, Kim IK, Park TG, Adv. Funct. Mater., 19(12), 1884 (2009)

[15] Lee H, Lee K, Park TG, Bioconjugate Chem., 19, 1319 (2008)

[16] Yokoyama A, Yokozawa T, Macromolecules, 40(12), 4093 (2007)

[17] Rao JP, Geckeler KE, Prog. Polym. Sci, 36, 887 (2011)

[18] Carrio A, Schwach G, Coudane J, Vert M, J. Control. Release, 37, 113 (1995)

[19] Hu P, Tirelli N, Bioconjugate Chem., 23, 438 (2012)

[20] Baciocchi E, Del Giacco T, Giombolini P, Lanzalunga O, Tetrahedron, 62, 6566 (2006)

[21] Winterbourn C, Metodiewa D, Free Radic. Biol. Med., 27, 322 (1999)

[22] Asada K, Kanematsu S, Agric. Biol. Chem. Tokyo, 40, 1891 (1976)

[23] Aruoma OI, Halliwell B, Hoey BM, Butler J, Free Radic. Biol. Med., 6, 593 (1989)

[24] Hussain SP, Hofseth LJ, Harris CC, Nat. Rev. Cancer, 3, 276 (2003)

[25] Albini A, Sporn MB, Nat. Rev. Cancer, 7, 139 (2007)

[26] Nam YS, Yoon JJ, Lee JG, Park TG, J. Biomater. Sci. Polym. Ed., 10, 1145 (1999)

[27] Shim MS, Xia Y, Angew. Chem.-Int. Edit., 52, 6926 (2013)

[28] Kumar B, Koul S, Khandrika L, Meacham RB, Koul HK, Cancer Res., 68, 1777 (2008)